AMPA/kainate receptor activation inhibits neuronal delayed rectifier K+ current via Na+ entry in rat cortical neurons.
In the present study we evaluated the modulation of neuronal delayed rectifier K+ current (IK) by activation of ionotropic glutamate receptors. In whole-cell voltage-clamp experiments, an external application of 10-100 microM kainate suppressed the amplitude of IK following an inward shift of holding current. The effect of kainate on IK was eliminated by CN QX, an AMPA/kainate receptor antagonist, indicating that the receptor-mediated cation entry caused IK suppression. When external Na+ was completely replaced by equimolar choline+ or N-methyl-D-glucamine, kainate-induced IK suppression was abolished. Our results suggest that in cultured rat cortical neurons, AMPA/kainate receptor activation leads to an intracellular Na+ increase which blocks delayed rectifier K+ channels. This contributes to feed-forward excitation of neuronal cells in glutaminergic responses.
Houzen
H
H
Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan. hohzen@med.hokudai.ac.jp
Kanno
M
M
Kikuchi
S
S
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000502:physiology; D002478:Cells, Cultured; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D008536:Meglumine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D026902:Potassium Channel Blockers; D018091:Receptors, AMPA; D008536:Meglumine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D012964:Sodium; D007608:Kainic Acid